Design and evaluation of a skin-on-a-chip pumpless microfluidic device.

The development of microfluidic culture technology facilitates the progress of study of cell and tissue biology. This technology expands the understanding of pathological and physiological changes. A skin chip, as in vitro model, consisting of normal skin tissue with epidermis and dermis layer (full thickness) was developed. Polydimethylsiloxane microchannels with a fed-batched controlled perfusion feeding system were used to create a full-thick ex-vivo human skin on-chip model. The design of a novel skin-on-a-chip model was reported, in which the microchannel structures mimic the architecture of the realistic vascular network as nutrients transporter to the skin layers. Viabilities of full-thick skin samples cultured on the microbioreactor and traditional tissue culture plate revealed that a precise controlled condition provided by the microfluidic enhanced tissue viability at least for seven days. Several advantages in skin sample features under micro-scale-controlled conditions were found such as skin mechanical strength, water adsorption, skin morphology, gene expression, and biopsy longevity. This model can provide an in vitro environment for localizing drug delivery and transdermal drug diffusion studies. The skin on the chip can be a valuable in vitro model for representing the interaction between drugs and skin tissue and a realistic platform for evaluating skin reaction to pharmaceutical materials and cosmetic products.

Carboxymethyl Chitosan-Functionalized Polyaniline/Polyacrylonitrile Nano-Fibers for Neural Differentiation of Mesenchymal Stem Cells.

Electroconductive scaffolds based on polyaniline (PANi)/polyacrylonitrile (PAN) were fabricated and surface-functionalized by carboxymethyl chitosan (CMC) as efficient scaffolds for nerve tissue regeneration. The results of scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, and water contact angle measurement approved the successful fabrication of CMC-functionalized PANi/PAN-based scaffolds. Human adipose-derived mesenchymal stem cells (hADMSCs) were cultured on the scaffolds for 10 d in the presence or absence of ß-carotene (ßC, 20 µM) as a natural neural differentiation agent. The MTT and SEM results confirmed the attachment and proliferation of hADMSCs on the scaffolds. The expression of MAP2 at the mRNA and protein levels showed the synergic neurogenic induction effect of CMC-functionalization and ßC for hADMSCs on the scaffolds. The CMC-functionalized nanofibrous PANi/PAN-based scaffolds are potential candidates for nerve tissue engineering.

The Dibenzyl Isoquinoline Alkaloid Berbamine Ameliorates Osteoporosis by Inhibiting Bone Resorption.

Postmenopausal osteoporosis (PMOP) is a kind of primary osteoporosis that is characterized by decreased bone density and strength. Berbamine is a nonbasic quaternary benzylisoquinoline plant alkaloid that has been widely used in the clinic to treat leukopenia in China. We found that berbamine inhibited RANKL-induced osteoclastogenesis of bone marrow-derived macrophages (BMMs) in vitro, which mainly occurred in the middle phase and late phase. The gene and protein expression levels of osteoclast-related molecules, including CTSK, MMP-9, NFATc1, CD44 and DC-STAMP, were also downregulated by berbamine. In vivo, we treated PMOP mice with berbamine for 8 weeks and found that the extent of osteoporosis was alleviated significantly according to micro-CT scanning, hematoxylin-eosin staining, DC-STAMP immunohistochemical staining and TRAP immunohistochemical staining in the distal femurs of the mice. Our findings demonstrate that berbamine has an inhibitory effect on the osteoclastogenesis of BMMs and can prevent bone loss after ovariectomy in vivo. This study provides evidence that berbamine is a potential drug for the prevention and treatment of PMOP.

Cold atmospheric plasma modification and electrical conductivity induction in gelatin/polyvinylidene fluoride nanofibers for neural tissue engineering.

BACKGROUND: This research follows some investigations through neural tissue engineering, including fabrication, surface treatment, and evaluation of novel self-stimuli conductive biocompatible and degradable nanocomposite scaffolds. METHODS: Gelatin as a biobased material and polyvinylidene fluoride (PVDF) as a mechanical, electrical, and piezoelectric improvement agent were co-electrospun. In addition, polyaniline/graphene (PAG) nanoparticles were synthesized and added to gelatin solutions in different percentages to induce electrical conductivity. After obtaining optimum PAG percentage, cold atmospheric plasma (CAP) treatment was applied over the best samples by different plasma variable parameters. Finally, the biocompatibility of the scaffolds was analyzed and approved by in vitro tests using two different PC12 and C6 cell lines. In the present study the morphology, FTIR, dynamic light scattering, mechanical properties, wettability, contact angle tests, differential scanning calorimetric, rate of degradation, conductivity, biocompatibility, gene expression, DAPI staining, and cell proliferation were investigated. RESULTS: The PAG percentage optimization results revealed fiber diameter reduction, conductivity enhancement, young's modulus improvement, hydrophilicity devaluation, water uptake decrement, and degradability reduction in electrospun nanofibers by increasing the PAG concentration. Furthermore, ATR-FTIR, FE-SEM, AFM, and contact angle tests revealed that helium CAP treatment improves scaffold characterizations for 90 s in duration time. Furthermore, the results of the MTT assay, FE-SEM, DAPI staining, and RT-PCR revealed that samples containing 2.5% w/w of PAG are the most biocompatible, and CAP treatment increases cell proliferation and improves neural gene expression in the differentiation medium. CONCLUSIONS: According to the results, the samples with the 2.5% w/w of PAG could provide a suitable matrix for neural tissue engineering in terms of physicochemical and biological.

Neuronal differentiation of mesenchymal stem cells by polyvinyl alcohol/Gelatin/crocin and beta-carotene.

BACKGROUND: Nerve tissues are important in coordinating the motions and movements of the body. Nerve tissue repair and regeneration is a slow process that might take a long time and cost a lot of money. As a result, tissue engineering was employed to treat nerve tissue lesions. The aim of this study was to investigate the proliferation of C6 cells and human mesenchymal stem cells derived bone marrow (hBMMSCs) differentiate into neuronal-like cells on the polyvinyl alcohol/gelatin/crocin (PVA/Gel/Cro) nanofiber scaffolds in vitro. METHODS: PVA/Gel scaffolds containing crocin in three concentrations (1%, 3%, and 5%) were prepared by the electrospinning method. The human bone marrow-derived mesenchymal stem cells (hBMSCs) differentiation on the PVA/Gel/Cro 5% that induced by beta-carotene (ßC), was analyzed during 10 days. Morphology of differentiated cells on the scaffolds was taken by scanning electron microscope (SEM). The expression of the neural cell markers was studied by quantitative reverse transcription- polymerase chain reaction (qRT-PCR) and immunocytochemistry (ICC). RESULTS: MTT results of C6 cells culture on the scaffolds showed that proliferation and metabolic activity on PVA/Gel scaffold containing crocin 5% (PVA/Gel/Cro 5%) are significantly more than the other concentrations (P = 0.01). MSC differentiation to nerve-like cells was approved by MAP-2 expression at the mRNA level and NESTIN and MAP-2 at the protein level. CONCLUSIONS: These results suggested that PVA/Gel/Cro 5% and ßC could lead to hBMSCs differentiation to neural cells.